title: From caffeine to fish waste: amine compounds present in food and drugs and their interactions with primary amine oxidase.
abstract: Tissue bound primary amine oxidase (PrAO) and its circulating plasma-soluble form are involved, through their catalytic activity, in important cellular roles, including the adhesion of lymphocytes to endothelial cells during various inflammatory conditions, the regulation of cell growth and maturation, extracellular matrix deposition and maturation and glucose transport. PrAO catalyses the oxidative deamination of several xenobiotics and has been linked to vascular toxicity, due to the generation of cytotoxic aldehydes. In this study, a series of amines and aldehydes contained in food and drugs were tested via a high-throughput assay as potential substrates or inhibitors of bovine plasma PrAO. Although none of the compounds analyzed were found to be substrates for the enzyme, a series of molecules, including caffeine, the antidiabetics phenformin and tolbutamide and the antimicrobial pentamidine, were identified as PrAO inhibitors. Although the inhibition observed was in the millimolar and micromolar range, these data show that further work will be necessary to elucidate whether the interaction of ingested biogenic or xenobiotic amines with PrAO might adversely affect its biological roles.
authors.affiliation: School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. oliviera@tcd.ie
authors.forename: Aldo
authors.initials: A
authors.lastname: Olivieri
authors.forename: Daniel
authors.initials: D
authors.lastname: Rico
authors.forename: Zhied
authors.initials: Z
authors.lastname: Khiari
authors.forename: Gary
authors.initials: G
authors.lastname: Henehan
authors.forename: Jeff
authors.initials: J
authors.lastname: O'Sullivan
authors.forename: Keith
authors.initials: K
authors.lastname: Tipton
mesh_terms: D000588:Amines / Q000009:adverse effects* / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000009:adverse effects / Q000378:metabolism; D002417:Cattle; D004353:Drug Evaluation, Preclinical / Q000379:methods; D057075:Enzyme Assays / Q000379:methods; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000378:metabolism; D005396:Fish Products / Q000009:adverse effects; D005399:Fishes; D005502:Food / Q000009:adverse effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000378:metabolism; D050891:Oxidoreductases Acting on CH-NH2 Group Donors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010629:Phenformin / Q000009:adverse effects / Q000378:metabolism; D015262:Xenobiotics / Q000009:adverse effects / Q000378:metabolism
chemical_list: D000588:Amines; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D015262:Xenobiotics; D002110:Caffeine; D010629:Phenformin; D050891:Oxidoreductases Acting on CH-NH2 Group Donors